Clinical and pathological evidence suggest the existence of a diabetic cardiomyopathy in man. However, studies of myocardial function in diabetic and in experimental models of diabetes have been limited and the data inconclusive. During the first 2 years of HL 20426-02 entitled "Myocardial Function in Diabetes" we have shown in a model of severe drug-induced diabetes in rats that depressions of contractility and marked slowing of relaxation are demonstrable after only four weeks of diabetes. In addition preliminary experiments have also shown reduced activity of the Actomyosin ATPase and reduced calcium binding and uptake of the sarcoplasmic reticulum from diabetic cardiac muscle. Accordingly the proposed competitive renewal is designed to further characterize mechanical correlates of diabetic cardiac muscle activation, contraction, relaxation, and compliance with standard isotonic as well as servo-controlled techniques. Mechanisms responsible for the observed myocardial abnormalities in diabetes will be studied with parallel investigation of contractile protein biochemistry and in vitro sarcoplasmic reticulum function in diabetic hearts. Further morphologic, electronmicroscopic and histochemical studies of diabetic myocardium will be done to provide necessary structure-function correlations. The effects of insulin treatment either in the form of chronic insulin administration or isotransplantation of fetal pancreas to diabetic recipients, on the mechanics, biochemistry and structure of diabetic myocardium will be studied. The comparative aspects of diabetes will be studied in the rabbit during the later stages of the proposal. These further studies will add significantly to our current understanding of the myocardial effects of diabetes in a reproducible and well-characterized experimental model.